So far as the origin of androgenic alopecia, many theories are exposited such as (1) imbalance of hormones, (2) genetics, (3) circulatory failure, (4) nutrition. And it has been suggested that testosterone (androgenic hormone) played an important role on the generation of hairs. The relation between testosterone and androgenic alopecia is as follows:
Large quantities of metabolites by 5.alpha.-reductase such as DHT etc. in hair follicles of androgenic alopecia-patient exist more than that in females or healthy males. J. Clin. Endocr., 38, 811(1974)!.
It was reported that DHT converted from testosterone by 5.alpha.-reductase also plays an important physiological role in the generation of acnes (acne, pimple etc.) other than androgenic alopecia Br. J. Dermatol., 91, 123(1974); J. Invest. Dermatol., 56, 366(1971)!.
It has been clear that DHT also plays an important role in the generation and the development of prostatic hypertrophy J. Steroid Biochemistry, 11, 609(1979); J. Clinical Endocrinol and Metabolism, 56, 139(1983)!.
And, it is thought that DHT is also related to prostatic cancer.
Recently, it was confirmed that the existence of at least two 5.alpha.-reductase isozymes (I type and II type) in human. There are differences between these isozymes about gene formation, of course, biochemical properties, expression styles, hereditary properties and pharmacological properties. Nature, 354, 159-161(1991); J. Clin, Invest., 89,293-300(1992)!. Among two type isozymes, it is considered that II type one exists more than I type one in human testis.
Therefore, it was confirmed that inhibition of a change from testosterone to DHT by 5.alpha.-reductase inhibitor is useful for above diseases.
Now, research and development of 5.alpha.-reductase inhibitors are carried out energetically. Many kinds of compounds are synthesized and tested. 5.alpha.-Reductase inhibitors are largely divided into compounds having steroidal structure and compounds having non-steroidal structure.
A representation of steroidal compound is finasteride, shown by below formula, and the compound is available in the market. ##STR3##
As a non-steroidal compound, ONO-3805 shown below formula is known. ##STR4##